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Dichotomous metabolic networks govern human ILC2 proliferation and function
- Source :
- Nature Immunology, Nature Immunology, 2021, 22 (11), pp.1367-1374. ⟨10.1038/s41590-021-01043-8⟩, Nature Immunology, Nature Publishing Group, 2021, 22 (11), pp.1367-1374. ⟨10.1038/s41590-021-01043-8⟩
- Publication Year :
- 2021
-
Abstract
- Group 2 innate lymphoid cells (ILC2s) represent innate homologs of type 2 helper T cells (TH2) that participate in immune defense and tissue homeostasis through production of type 2 cytokines. While T lymphocytes metabolically adapt to microenvironmental changes, knowledge of human ILC2 metabolism is limited, and its key regulators are unknown. Here, we show that circulating ‘naive’ ILC2s have an unexpected metabolic profile with a higher level of oxidative phosphorylation (OXPHOS) than natural killer (NK) cells. Accordingly, ILC2s are severely reduced in individuals with mitochondrial disease (MD) and impaired OXPHOS. Metabolomic and nutrient receptor analysis revealed ILC2 uptake of amino acids to sustain OXPHOS at steady state. Following activation with interleukin-33 (IL-33), ILC2s became highly proliferative, relying on glycolysis and mammalian target of rapamycin (mTOR) to produce IL-13 while continuing to fuel OXPHOS with amino acids to maintain cellular fitness and proliferation. Our results suggest that proliferation and function are metabolically uncoupled in human ILC2s, offering new strategies to target ILC2s in disease settings.<br />ILC2 metabolism has been largely unexplored. Di Santo and colleagues examine metabolic profiles from naive and cytokine-activated ILC2s and find that IL-33-triggered ILC2s rely on distinct metabolic pathways to sustain proliferation and function.
- Subjects :
- Letter
Mitochondrial Diseases
Lymphocyte Activation
0302 clinical medicine
Immunology and Allergy
Glycolysis
Receptor
Tissue homeostasis
Cells, Cultured
0303 health sciences
MESH: Cytokines
Innate lymphoid cell
MESH: Energy Metabolism
MESH: Arginine
MESH: Mitochondrial Diseases
MESH: Case-Control Studies
Cell biology
Mitochondria
Phenotype
[SDV.IMM]Life Sciences [q-bio]/Immunology
Cytokines
MESH: Immunity, Innate
MESH: Cells, Cultured
MESH: Interleukin-33
MESH: Mitochondria
Immunology
Innate lymphoid cells
Oxidative phosphorylation
Biology
MESH: Phenotype
Arginine
03 medical and health sciences
Th2 Cells
MESH: Th2 Cells
MESH: Cell Proliferation
Humans
MESH: Lymphocyte Activation
PI3K/AKT/mTOR pathway
030304 developmental biology
Cell Proliferation
MESH: Humans
Interleukins
Metabolism
Interleukin-33
Immunity, Innate
Metabolic pathway
Case-Control Studies
Energy Metabolism
Amino Acids, Branched-Chain
030215 immunology
MESH: Amino Acids, Branched-Chain
Subjects
Details
- ISSN :
- 15292908 and 15292916
- Database :
- OpenAIRE
- Journal :
- Nature Immunology
- Accession number :
- edsair.doi.dedup.....e072b6d889432eb5d0e60a3fe6f3aa3b
- Full Text :
- https://doi.org/10.1038/s41590-021-01043-8